tbuckley/cabot-search huggingface dataset:
Factors Associated With False-Positive Recalls in Mammography Screening
Authors: Xinhe Mao, Wei He, Keith Humphreys, Mikael Eriksson, Natalie Holowko, Fredrik Strand, Per Hall, Kamila Czene
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: We aimed to identify factors associated with false-positive recalls in mammography screening compared with women who were not recalled and those who received true-positive recalls. Methods: We included 29,129 women, aged 40 to 74 years, who participated in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) between 2011 and 2013 with follow-up until the end of 2017. Nonmammographic factors were collected from questionnaires, mammographic factors were generated from mammograms, and genotypes were determined using the OncoArray or an Illumina custom array. By the use of conditional and regular logistic regression models, we investigated the association between breast cancer risk factors and risk models and false-positive recalls. Results: Women with a history of benign breast disease, high breast density, masses, microcalcifications, high Tyrer-Cuzick 10-year risk scores, KARMA 2-year risk scores, and polygenic risk scores were more likely to have mammography recalls, including both false-positive and true-positive recalls. Further analyses restricted to women who were recalled found that women with a history of benign breast disease and dense breasts had a similar risk of having false-positive and true-positive recalls, whereas women with masses, microcalcifications, high Tyrer-Cuzick 10-year risk scores, KARMA 2-year risk scores, and polygenic risk scores were more likely to have true-positive recalls than false-positive recalls. Conclusions: We found that risk factors associated with false-positive recalls were also likely, or even more likely, to be associated with true-positive recalls in mammography screening.
Prevalent Pseudoprogression and Pseudoresidue in Patients With Rectal Cancer Treated With Neoadjuvant Immune Checkpoint Inhibitors
Authors: Yumo Xie, Jinxin Lin, Ning Zhang, Xiaolin Wang, Puning Wang, Shaoyong Peng, Juan Li, Yuanhui Wu, Yaoyi Huang, Zhuokai Zhuang, Dingcheng Shen, Mingxuan Zhu, Xiaoxia Liu, Guangjian Liu, Xiaochun Meng, Meijin Huang, Huichuan Yu, Yanxin Luo
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping organ preservation in rectal cancer. However, the benefits are accompanied by distinctive patterns of response, introducing a dilemma in the response evaluation for clinical decision-making. Patients and Methods: Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features. Results: Among the 13 patients receiving nICI treatment, in the final radiologic evaluation prior to surgery (at a median of 103 days after initiation of therapy), progressive disease (n=3), stable disease (n=1), partial response (n=7), and complete response (n=2) were observed. However, these patients were later confirmed as having pathologic complete response, resulting in pseudoprogression and pseudoresidue with incidences of 23.1% (n=3) and 76.9% (n=10), respectively, whereas no pseudoprogression was found in the 13 patients receiving nCRT. We further revealed the histopathologic basis underlying the pseudoprogression and pseudoresidue by discovering the distinctive immune-related regression features after nICI treatment, including fibrogenesis, dense lymphocytes, and plasma cell infiltration. Conclusions: Pseudoprogression and pseudoresidue were unique and prevalent response patterns in MSI-H/dMMR rectal cancer after nICI treatment. Our findings highlight the importance of developing specific strategies for response evaluation in neoadjuvant immunotherapy to identify patients with a good response in whom sphincter/organ-preserving or watch-and-wait strategies may be considered.
NCCN News
Journal: Journal of the National Comprehensive Cancer Network (2023)

CancersNCCN is working on new NCCN Harmonized Guidelines for Sub-Saharan Africa, in collaboration with the African Cancer Coalition (ACC), the American Cancer Society (ACS), and the Clinton Health Access Initiative (CHAI).The organizations are part of Allied Against Cancer, a global multisector effort to improve resource-stratified access to life-saving cancer care in Sub-Saharan Africa.These harmonized guidelines build on the successful implementation of evidencebased, expert consensus context-appropriate recommendations for managing nearly all adult cancers across more than a dozen countries throughout the region.The groups recently reunited in Dar es Salaam, Tanzania, to launch 4 additional NCCN Harmonized Guidelines specifically focused on best practices for treating children with cancer.NCCN Harmonized Guidelines use color-coded recommendations for optimal cancer care in high-resource settings alongside pragmatic modifications for effective treatment options in low-and mid-resource settings.The guidelines are established in collaboration with local health ministries, providers, and advocates, and are based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)-a recognized standard for clinical direction and policy in cancer management worldwide.NCCN Harmonized Guidelines for Sub-Saharan Africa are available for free at NCCN.org/harmonized or via the Virtual Library of NCCN Guidelines App."With approximately 90% of childhood cancers occurring in low-to middleincome countries (LMICs), the need for harmonized treatment guidelines for Sub-Saharan Africa for this unique population is paramount," said Dr. Edith Matsikidze, Oncologist at Parirenyatwa Hospital in Zimbabwe and member of the African Cancer Coalition."The collaborations between African experts working together with experts from NCCN will greatly contribute toward standard treatment practices across the African continent.The NCCN Harmonized Guidelines have come at the right time, as we work towards achieving the Global Initiative for Childhood Cancer (GICC) goal of at least a 60% survival rate for childhood cancer in LMICs.The implementation of affordable, available, high-impact, and evidence-based interventions-as outlined in these guidelines-is a pragmatic solution that I would recommend for immediate adoption."The new pediatric guidelines will cover: Pediatric B-cell lymphomas (ie, non-Hodgkin lymphomas, including Burkitt lymphoma) Pediatric central nervous system (CNS) cancers Pediatric Hodgkin lymphoma Wilms tumor xiv
Understanding Disparities: A Case Illustrative of the Struggles Facing Transgender and Gender Diverse Patients With Cancer
Authors: Elizabeth J. Cathcart-Rake, Juliana M. Kling, Evelyn F. Carroll, Caroline Davidge-Pitts, Jennifer Le-Rademacher, Jennifer L. Ridgeway, Cesar A. Gonzalez, Aminah Jatoi
Journal: Journal of the National Comprehensive Cancer Network (2023)

2][3][4][5] Improving the poorer cancer outcomes among TGD individuals is important.The first step to mitigating these disparities is identifying TGD people in the electronic health record (EHR) and discussing individual needs and preferences at the point of care.The cancer-specific needs of TGD people and the challenges of identifying these needs to adequately address them are noteworthy, 2,3 as highlighted in the following case.A 48-year-old nonbinary person with no contributory medical or family history was diagnosed with a locally advanced, estrogen receptor-positive, progesterone receptor-negative, HER2-negative breast cancer.The patient elected to pursue bilateral mastectomy without reconstruction, an axillary lymph node dissection, and then adjuvant chemotherapy and endocrine therapy.At the initial oncology appointment, the patient requested that a different version of their first name ("Eli", changed here to protect anonymity) be used during the clinic visit and that no specific male or female pronouns be used.Although Eli shared Eli's nonbinary identity with the treating oncologist, Eli did not wish to disclose Eli's gender identity with their other clinicians.Eli's sex assigned at birth (SAB) was clearly identifiable throughout the medical record due to the SAB-specific nature of treatments for Eli's cancer (such as utilization of ovarian function suppression), and therefore the patient requested that both SAB and gender identity remain as female within the EHR.Throughout the patient's clinical course, other members of their cancer care team used female pronouns both with the patient and to describe the patient in medical discussion and in the medical record.Eli's concerns for privacy and safety were paramount.Eli noted feeling that their decision to pursue bilateral mastectomy without reconstruction was questioned by numerous members of the healthcare team both prior to and following their surgery.Although the patient found bilateral mastectomy to be a gender-affirming surgery, Eli reported being told by clinicians that Eli would regret the lack of implant-based reconstruction in the future.The patient felt judged by clinicians who used euphemisms such as "you won't look the same in a swimsuit," implying that such a surgery would make their outward appearance less stereotypically feminine.Although we present this single case, there are likely a number of patients who experience gender-related struggles after a cancer diagnosis; these have not yet been well-captured.
Androgen Deprivation Therapy and Risk of Cardiovascular Disease in Patients With Prostate Cancer Based on Existence of Cardiovascular Risk
Authors: Alice Dragomir, Nawar Touma, Jason Hu, Sylvie Perreault, Armen G. Aprikian
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. Patients and Methods : Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. Results : Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69–81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26–0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11–0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63–3.36). Conclusions: Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.
Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer
Authors: Sushmita Gordhandas, William A. Zammarrelli, Eric V. Rios-Doria, Angela K. Green, Vicky Makker
Journal: Journal of the National Comprehensive Cancer Network (2023)

Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.
Engine shutdown: migrastatic strategies and prevention of metastases
Authors: Martina Raudenská, Kateřina Petrláková, Tamara Juriňáková, Jindřiška Leischner Fialová, Michaela Fojtů, Milan Jakubek, Daniel Rösel, Jan Brábek, Michal Masařík
Journal: Trends in cancer (2023)

Most cancer-related deaths among patients with solid tumors are caused by metastases. Migrastatic strategies represent a unique therapeutic approach to prevent all forms of cancer cell migration and invasion. Because the migration machinery has been shown to promote metastatic dissemination, successful migrastatic therapy may reduce the need for high-dose cytotoxic therapies that are currently used to prevent the risk of metastatic dissemination. In this review we focus on anti-invasive and antimetastatic strategies that hold promise for the treatment of solid tumors. The best targets for migrastatic therapy would be those that are required by all forms of motility, such as ATP availability, mitochondrial metabolism, and cytoskeletal dynamics and cell contractility.
Single-cell Deconvolution of a Specific Malignant Cell Population as a Poor Prognostic Biomarker in Low-risk Clear Cell Renal Cell Carcinoma Patients
Authors: Judikael R. Saout, Gwendoline Lecuyer, Simon Léonard, Bertrand Evrard, Solène-Florence Kammerer-Jacquet, Laurence Noël, Zine-Eddine Khene, Romain Mathieu, Angélique Brunot, Antoine D. Rolland, Karim Bensalah, Nathalie Rioux-Leclercq, Aurélie Lardenois, Frédéric Chalmel
Journal: European Urology (2023)
Reply to O. Devlin et al
Authors: Sunandana Chandra, Jacob S. Choi, Jeffrey A. Sosman
Journal: Journal of Clinical Oncology (2023)

have made an incredibly important point in response to the publication of the SECOMBIT trial which investigated the sequencing of immunotherapy and targeted therapy (TT) in the management of patients with treatment-naive BRAF-mutant metastatic melanoma and to our subsequent editorial on the trial results. 2 The SECOMBIT trial with its differing sequencing schemas, included a sandwich arm and proposed that an initial induction course of TT, followed by combination immune checkpoint inhibitors (ICIs), may be a way to enhance initial response rates while maintaining long-term benefit in patients with advanced melanoma.
Pharmacology of Heparin and Related Drugs: An Update
Authors: John Hogwood, Barbara Mulloy, Rebeca Lever, Elaine Gray, Clive P. Page
Journal: Pharmacological Reviews (2023)

Heparin has been used extensively as an antithrombotic and anticoagulant for close to 100 years. This anticoagulant activity is attributed mainly to the pentasaccharide sequence, which potentiates the inhibitory action of antithrombin, a major inhibitor of the coagulation cascade. More recently it has been elucidated that heparin exhibits anti-inflammatory effect via interference of the formation of neutrophil extracellular traps and this may also contribute to heparin9s antithrombotic activity. This illustrates that heparin interacts with a broad range of biomolecules, exerting both anticoagulant and nonanticoagulant actions. Since our previous review, there has been an increased interest in these nonanticoagulant effects of heparin, with the beneficial role in patients infected with SARS2-coronavirus a highly topical example. This article provides an update on our previous review with more recent developments and observations made for these novel uses of heparin and an overview of the development status of heparin-based drugs. <h3>Significance Statement</h3> This state-of-the-art review covers recent developments in the use of heparin and heparin-like materials as anticoagulant, now including immunothrombosis observations, and as nonanticoagulant including a role in the treatment of SARS-coronavirus and inflammatory conditions.
Scale-sensitivity in the measurement and interpretation of environmental niches
Authors: Muyang Lu, Walter Jetz
Journal: Trends in Ecology & Evolution (2023)

Species environmental niches are central to ecology, evolution, and global change research, but their characterization and interpretation depend on the spatial scale (specifically, the spatial grain) of their measurement. We find that the spatial grain of niche measurement is usually uninformed by ecological processes and varies by orders of magnitude. We illustrate the consequences of this variation for the volume, position, and shape of niche estimates, and discuss how it interacts with geographic range size, habitat specialization, and environmental heterogeneity. Spatial grain significantly affects the study of niche breadth, environmental suitability, niche evolution, niche tracking, and climate change effects. These and other fields will benefit from a more mechanism-informed choice of spatial grain and cross-grain evaluations that integrate different data sources.
Conformity and differentiation are two sides of the same coin
Authors: Christos C. Ioannou, Kate L. Laskowski
Journal: Trends in Ecology & Evolution (2023)

Variation between individuals is a key component of selection and hence evolutionary change. Social interactions are important drivers of variation, potentially making behaviour more similar (i.e., conform) or divergent (i.e., differentiate) between individuals. While documented across a wide range of animals, behaviours and contexts, conformity and differentiation are typically considered separately. Here, we argue that rather than independent concepts, they can be integrated onto a single scale that considers how social interactions drive changes in interindividual variance within groups: conformity reduces variance within groups while differentiation increases it. We discuss the advantages of placing conformity and differentiation at different ends of a single scale, allowing for a deeper understanding of the relationship between social interactions and interindividual variation.
Data-driven longitudinal characterization of neonatal health and morbidity
Authors: Davide De Francesco, Jonathan D. Reiss, Jacquelyn Roger, Alice S. Tang, Alan L. Chang, Martin Becker, Thanaphong Phongpreecha, Camilo Espinosa, Susanna Morin, Eloïse Berson, Melan Thuraiappah, Brian L. Le, Neal G. Ravindra, Seyedeh Neelufar Payrovnaziri, Samson Mataraso, Yeasul Kim, Lei Xue, Melissa G. Rosenstein, Tomiko Oskotsky, Ivana Marić, Brice Gaudilliere, Brendan Carvalho, Brian T. Bateman, Martin S. Angst, Lawrence S. Prince, Yair J. Blumenfeld, William E. Benitz, Janene H. Fuerch, Gary M. Shaw, Karl G. Sylvester, David K. Stevenson, Marina Sirota, Nima Aghaeepour
Journal: Science Translational Medicine (2023)

Although prematurity is the single largest cause of death in children under 5 years of age, the current definition of prematurity, based on gestational age, lacks the precision needed for guiding care decisions. Here, we propose a longitudinal risk assessment for adverse neonatal outcomes in newborns based on a deep learning model that uses electronic health records (EHRs) to predict a wide range of outcomes over a period starting shortly before conception and ending months after birth. By linking the EHRs of the Lucile Packard Children’s Hospital and the Stanford Healthcare Adult Hospital, we developed a cohort of 22,104 mother-newborn dyads delivered between 2014 and 2018. Maternal and newborn EHRs were extracted and used to train a multi-input multitask deep learning model, featuring a long short-term memory neural network, to predict 24 different neonatal outcomes. An additional cohort of 10,250 mother-newborn dyads delivered at the same Stanford Hospitals from 2019 to September 2020 was used to validate the model. Areas under the receiver operating characteristic curve at delivery exceeded 0.9 for 10 of the 24 neonatal outcomes considered and were between 0.8 and 0.9 for 7 additional outcomes. Moreover, comprehensive association analysis identified multiple known associations between various maternal and neonatal features and specific neonatal outcomes. This study used linked EHRs from more than 30,000 mother-newborn dyads and would serve as a resource for the investigation and prediction of neonatal outcomes. An interactive website is available for independent investigators to leverage this unique dataset: https://maternal-child-health-associations.shinyapps.io/shiny_app/ .
An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination
Authors: Juan Manuel Carreño, Ariel Raskin, Gagandeep Singh, Johnstone Tcheou, Hisaaki Kawabata, Charles Gleason, Komal Srivastava, Vladimir Vigdorovich, Nicholas Dambrauskas, Sneh Lata Gupta, Irene González Domínguez, Jose Luis Martinez, Stefan Slamanig, D. Noah Sather, Rama Raghunandan, Ponthip Wirachwong, Sant Muangnoicharoen, Punnee Pitisuttithum, Jens Wrammert, Mehul S. Suthar, Weina Sun, Peter Palese, Adolfo García-Sastre, Viviana Simon, Florian Krammer
Journal: Science Translational Medicine (2023)

NDV-HXP-S is a recombinant Newcastle disease virus–based vaccine against SARS-CoV-2, which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that used for the production of the vast majority of influenza virus vaccines. Here, we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a phase 1 clinical study in Thailand. The SARS-CoV-2 neutralizing and spike protein binding activity of NDV-HXP-S postvaccination serum samples was compared to that of samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of BNT162b2 vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccinees. This led us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios that were lower than those of BNT162b2 sera, suggesting that NDV-HXP-S vaccination elicits a high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induced an RBD-focused antibody response with little reactivity to S2. This finding may explain the high proportion of neutralizing antibodies. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers that are comparable to those elicited by mRNA vaccination.